Researchers began publishing the sequences of single cell genomes back in 2006 (Zhang et al., 2006), and the technology has continued to evolve until today (see Fan et al., 2010; Navin et al., 2011; Gundry et al., 2012; Hou et al., 2012; Wang et al., 2012). The improvement here lies in getting a smooth representation of the original DNA regions of the genome. Their method reduces variation and bias. This is very good for determining copy number variation. But another key component of accuracy (that the authors do not mention) is haplotype phase, which tells you if you have two mutations affecting both copies of a gene, or those same two mutations in only one copy, leaving the other copy unaffected. Knowing if you have one good copy or zero is a big deal for clinical (and research) accuracy. A combination of the MALBAC and long fragment read (LFR) methods would be ideal. Although previous work required more than one cell (Peters et al., 2012), note that here, Zong et al. also explicitly state, "our strategy to reduce the false positive rate was to sequence two or three kindred...  Read more

Researchers began publishing the sequences of single cell genomes back in 2006 (Zhang et al., 2006), and the technology has continued to evolve until today (see Fan et al., 2010; Navin et al., 2011; Gundry et al., 2012; Hou et al., 2012; Wang et al., 2012). The improvement here lies in getting a smooth representation of the original DNA regions of the genome. Their method reduces variation and bias. This is very good for determining copy number variation. But another key component of accuracy (that the authors do not mention) is haplotype phase, which tells you if you have two mutations affecting both copies of a gene, or those same two mutations in only one copy, leaving the other copy unaffected. Knowing if you have one good copy or zero is a big deal for clinical (and research) accuracy. A combination of the MALBAC and long fragment read (LFR) methods would be ideal. Although previous work required more than one cell (Peters et al., 2012), note that here, Zong et al. also explicitly state, "our strategy to reduce the false positive rate was to sequence two or three kindred cells derived from the same cell."

References:
Zhang K, Martiny AC, Reppas NB, Barry KW, Malek J, Chisholm SW, Church GM. Sequencing genomes from single cells by polymerase cloning. Nat Biotechnol. 2006 Jun;24(6):680-6. Abstract

Fan HC, Wang J, Potanina A, Quake SR. Whole-genome molecular haplotyping of single cells. Nat Biotechnol. 2011 Jan;29(1):51-7. Abstract

Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M. Tumour evolution inferred by single-cell sequencing. Nature. 2011 Apr 7;472(7341):90-4. Abstract

Gundry M, Li W, Maqbool SB, Vijg J. Direct, genome-wide assessment of DNA mutations in single cells. Nucleic Acids Res. 2012 Mar;40(5):2032-40. Abstract

Hou Y, Song L, Zhu P, Zhang B, Tao Y, Xu X, Li F, Wu K, Liang J, Shao D, Wu H, Ye X, Ye C, Wu R, Jian M, Chen Y, Xie W, Zhang R, Chen L, Liu X, Yao X, Zheng H, Yu C, Li Q, Gong Z, Mao M, Yang X, Yang L, Li J, Wang W, Lu Z, Gu N, Laurie G, Bolund L, Kristiansen K, Wang J, Yang H, Li Y, Zhang X, Wang J. Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm. Cell. 2012 Mar 2;148(5):873-85. Abstract

Wang J, Fan HC, Behr B, Quake SR. Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell. 2012 Jul 20;150(2):402-12. Abstract

Peters BA, Kermani BG, Sparks AB, Alferov O, Hong P, Alexeev A, Jiang Y, Dahl F, Tang YT, Haas J, Robasky K, Zaranek AW, Lee JH, Ball MP, Peterson JE, Perazich H, Yeung G, Liu J, Chen L, Kennemer MI, Pothuraju K, Konvicka K, Tsoupko-Sitnikov M, Pant KP, Ebert JC, Nilsen GB, Baccash J, Halpern AL, Church GM, Drmanac R. Accurate whole-genome sequencing and haplotyping from 10 to 20 human cells. Nature. 2012 Jul 11;487(7406):190-5. Abstract

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